{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:47:34Z","timestamp":1788299254301,"version":"build-2803163510"},"reference-count":114,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NICHD","award":["HD100529"],"award-info":[{"award-number":["HD100529"]}]},{"name":"NIH\/NICHD","award":["HD100529-02S1"],"award-info":[{"award-number":["HD100529-02S1"]}]},{"name":"NIH\/NICHD","award":["HD101852"],"award-info":[{"award-number":["HD101852"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent studies have demonstrated that somatic MED12 mutations in exon 2 occur at a frequency of up to 80% and have a functional role in leiomyoma pathogenesis. The objective of this study was to elucidate the expression profile of coding RNA transcripts in leiomyomas, with and without these mutations, and their paired myometrium. Next-generation RNA sequencing (NGS) was used to systematically profile the differentially expressed RNA transcripts from paired leiomyomas (n = 19). The differential analysis indicated there are 394 genes differentially and aberrantly expressed only in the mutated tumors. These genes were predominantly involved in the regulation of extracellular constituents. Of the differentially expressed genes that overlapped in the two comparison groups, the magnitude of change in gene expression was greater for many genes in tumors bearing MED12 mutations. Although the myometrium did not express MED12 mutations, there were marked differences in the transcriptome landscape of the myometrium from mutated and non-mutated specimens, with genes regulating the response to oxygen-containing compounds being most altered. In conclusion, MED12 mutations have profound effects on the expression of genes pivotal to leiomyoma pathogenesis in the tumor and the myometrium which could alter tumor characteristics and growth potential.<\/jats:p>","DOI":"10.3390\/ijms24043742","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T07:01:23Z","timestamp":1676271683000},"page":"3742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas"],"prefix":"10.3390","volume":"24","author":[{"given":"Tsai-Der","family":"Chuang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7227-1032","authenticated-orcid":false,"given":"Jianjun","family":"Gao","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6371-8931","authenticated-orcid":false,"given":"Hayden","family":"McSwiggin","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drake","family":"Boos","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"},{"name":"Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Khorram","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA"},{"name":"The Lundquist Institute for Biomedical Innovation, Torrance, CA 90502, USA"},{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1111\/1471-0528.14640","article-title":"Epidemiology of uterine fibroids: A systematic review","volume":"124","author":"Stewart","year":"2017","journal-title":"Bjog"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/humupd\/dmx032","article-title":"Extracellular matrix in uterine leiomyoma pathogenesis: A potential target for future therapeutics","volume":"24","author":"Islam","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1055\/s-0030-1251476","article-title":"Proinflammatory and profibrotic mediators: Principal effectors of leiomyoma development as a fibrotic disorder","volume":"28","author":"Chegini","year":"2010","journal-title":"Semin. Reprod. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/humupd\/dmt058","article-title":"Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: Comprehensive review, conference summary and future recommendations","volume":"20","author":"Segars","year":"2014","journal-title":"Hum. Reprod. Update"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"183","DOI":"10.12688\/f1000research.6189.1","article-title":"Recent scientific advances in leiomyoma (uterine fibroids) research facilitates better understanding and management","volume":"4","author":"Taylor","year":"2015","journal-title":"F1000Res"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1177\/1933719117711265","article-title":"Expression Profiling of lncRNAs, miRNAs, and mRNAs and Their Differential Expression in Leiomyoma Using Next-Generation RNA Sequencing","volume":"25","author":"Chuang","year":"2018","journal-title":"Reprod. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8625","DOI":"10.18632\/oncotarget.2349","article-title":"Integrated analysis of long noncoding RNAs and mRNAs reveals their potential roles in the pathogenesis of uterine leiomyomas","volume":"5","author":"Guo","year":"2014","journal-title":"Oncotarget"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.fertnstert.2020.07.024","article-title":"Functional role of the long noncoding RNA X-inactive specific transcript in leiomyoma pathogenesis","volume":"115","author":"Chuang","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"bqab186","DOI":"10.1210\/endocr\/bqab186","article-title":"Long Noncoding RNA MIAT Modulates the Extracellular Matrix Deposition in Leiomyomas by Sponging MiR-29 Family","volume":"162","author":"Chuang","year":"2021","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1007\/s43032-021-00571-w","article-title":"Emerging Roles of Long Non-coding RNAs in Uterine Leiomyoma Pathogenesis: A Review","volume":"29","author":"Falahati","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1007\/s43032-022-00981-4","article-title":"Differential Expression of Super-Enhancer-Associated Long Non-coding RNAs in Uterine Leiomyomas","volume":"29","author":"Chuang","year":"2022","journal-title":"Reprod. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1007\/s00404-017-4515-5","article-title":"Epigenetic and genetic landscape of uterine leiomyomas: A current view over a common gynecological disease","volume":"296","author":"Lagana","year":"2017","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.fertnstert.2014.06.050","article-title":"Genomics of uterine leiomyomas: Insights from high-throughput sequencing","volume":"102","author":"Mehine","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1093\/hmg\/dds051","article-title":"Expression profiling of uterine leiomyomata cytogenetic subgroups reveals distinct signatures in matched myometrium: Transcriptional profilingof the t(12;14) and evidence in support of predisposing genetic heterogeneity","volume":"21","author":"Hodge","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/modpathol.2016.107","article-title":"Exploring chromosomal abnormalities and genetic changes in uterine smooth muscle tumors","volume":"29","author":"Heitzer","year":"2016","journal-title":"Mod. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1126\/science.1208930","article-title":"MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas","volume":"334","author":"Makinen","year":"2011","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1002\/ijc.27424","article-title":"MED12 mutations in uterine fibroids--their relationship to cytogenetic subgroups","volume":"131","author":"Markowski","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_18","first-page":"592","article-title":"Silencing Med12 Gene Reduces Proliferation of Human Leiomyoma Cells Mediated via Wnt\/beta-Catenin Signaling Pathway","volume":"158","author":"Laknaur","year":"2017","journal-title":"Endocrinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1007\/s43032-019-00084-7","article-title":"Introduction of Somatic Mutation in MED12 Induces Wnt4\/\u03b2-Catenin and Disrupts Autophagy in Human Uterine Myometrial Cell","volume":"27","author":"Ismail","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1042\/BST20180608","article-title":"Twenty years of Mediator complex structural studies","volume":"47","author":"Verger","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/cncr.32672","article-title":"The emerging role of mediator complex subunit 12 in tumorigenesis and response to chemotherapeutics","volume":"126","author":"Zhang","year":"2020","journal-title":"Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/s41598-017-01199-0","article-title":"Multiple clinical characteristics separate MED12-mutation-positive and -negative uterine leiomyomas","volume":"7","author":"Heinonen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1172\/JCI81534","article-title":"Med12 gain-of-function mutation causes leiomyomas and genomic instability","volume":"125","author":"Mittal","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.celrep.2014.03.047","article-title":"Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity","volume":"7","author":"Turunen","year":"2014","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1074\/jbc.RA118.001725","article-title":"Oncogenic exon 2 mutations in Mediator subunit MED12 disrupt allosteric activation of cyclin C-CDK8\/19","volume":"293","author":"Park","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.1128\/MCB.00443-06","article-title":"Mediator modulates Gli3-dependent Sonic hedgehog signaling","volume":"26","author":"Zhou","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.cell.2012.10.035","article-title":"MED12 controls the response to multiple cancer drugs through regulation of TGF-beta receptor signaling","volume":"151","author":"Huang","year":"2012","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1177\/1933719118768692","article-title":"Regulation of Cell Cycle Regulatory Proteins by MicroRNAs in Uterine Leiomyoma","volume":"26","author":"Chuang","year":"2019","journal-title":"Reprod. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.fertnstert.2019.07.1324","article-title":"Cross-talk between miR-29c and transforming growth factor-\u03b23 is mediated by an epigenetic mechanism in leiomyoma","volume":"112","author":"Chuang","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.fertnstert.2021.05.081","article-title":"Tryptophan catabolism is dysregulated in leiomyomas","volume":"116","author":"Chuang","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/molehr\/gau114","article-title":"Overexpression of the truncated form of High Mobility Group A proteins (HMGA2) in human myometrial cells induces leiomyoma-like tissue formation","volume":"21","author":"Mas","year":"2015","journal-title":"Mol. Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1210\/endrev\/bnab039","article-title":"Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment","volume":"43","author":"Yang","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1210\/me.2012-1075","article-title":"miR-93\/106b and their host gene, MCM7, are differentially expressed in leiomyomas and functionally target F3 and IL-8","volume":"26","author":"Chuang","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"633180","DOI":"10.3389\/fcell.2021.633180","article-title":"Understanding the Impact of Uterine Fibroids on Human Endometrium Function","volume":"9","author":"Navarro","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1530\/ERC-12-0007","article-title":"miR-200c is aberrantly expressed in leiomyomas in an ethnic-dependent manner and targets ZEBs, VEGFA, TIMP2, and FBLN5","volume":"19","author":"Chuang","year":"2012","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.1016\/j.celrep.2019.11.077","article-title":"Integrated Epigenome, Exome, and Transcriptome Analyses Reveal Molecular Subtypes and Homeotic Transformation in Uterine Fibroids","volume":"29","author":"George","year":"2019","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.matbio.2020.09.001","article-title":"Collagen XI regulates the acquisition of collagen fibril structure, organization and functional properties in tendon","volume":"94","author":"Sun","year":"2020","journal-title":"Matrix Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/nrc2761","article-title":"Mucins in cancer: Function, prognosis and therapy","volume":"9","author":"Kufe","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gawe\u0142, A.M., Ratajczak, M., Gajda, E., Grzanka, M., Paziewska, A., Cie\u015blicka, M., Kulecka, M., Oczko-Wojciechowska, M., and Godlewska, M. (2021). Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136726"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4348","DOI":"10.1016\/j.febslet.2014.10.012","article-title":"FERM domain-containing protein FRMD5 regulates cell motility via binding to integrin \u03b25 subunit and ROCK1","volume":"588","author":"Hu","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"769033","DOI":"10.3389\/fonc.2021.769033","article-title":"FCGBP Is a Prognostic Biomarker and Associated With Immune Infiltration in Glioma","volume":"11","author":"Yan","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"863317","DOI":"10.3389\/fimmu.2022.863317","article-title":"Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.7150\/ijms.45129","article-title":"The emerging role of EGFL6 in angiogenesis and tumor progression","volume":"17","author":"Kang","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1242\/jcs.00059","article-title":"Fibronectin at a glance","volume":"115","author":"Pankov","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1097\/IJG.0000000000000108","article-title":"Biology of the extracellular matrix: An overview","volume":"23","author":"Yue","year":"2014","journal-title":"J. Glaucoma"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1210\/er.2009-0034","article-title":"Kallikreins on steroids: Structure, function, and hormonal regulation of prostate-specific antigen and the extended kallikrein locus","volume":"31","author":"Lawrence","year":"2010","journal-title":"Endocr. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1111\/j.1742-4658.2009.07070.x","article-title":"Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein","volume":"276","author":"Kawaguchi","year":"2009","journal-title":"FEBS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.2174\/1381612828666220501165644","article-title":"ITGA9: Potential Biomarkers and Therapeutic Targets in Different Tumors","volume":"28","author":"Wu","year":"2022","journal-title":"Curr. Pharm. Des."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fnmol.2017.00199","article-title":"Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility","volume":"10","author":"Ayanlaja","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40364-021-00323-7","article-title":"The Wnt signaling pathway in tumorigenesis, pharmacological targets, and drug development for cancer therapy","volume":"9","author":"Wang","year":"2021","journal-title":"Biomark. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1038\/modpathol.2010.98","article-title":"Aberrant expression of selectin E, CXCL1, and CXCL13 in chronic endometritis","volume":"23","author":"Kitaya","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1500737","DOI":"10.1126\/sciadv.1500737","article-title":"Regulation of gene transcription by Polycomb proteins","volume":"1","author":"Aranda","year":"2015","journal-title":"Sci. Adv."},{"key":"ref_53","first-page":"178614","article-title":"S100A1: A regulator of striated muscle sarcoplasmic reticulum Ca2+ handling, sarcomeric, and mitochondrial function","volume":"2010","author":"Rohde","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fmolb.2020.00077","article-title":"Molecular Basis of S100A1 Activation and Target Regulation Within Physiological Cytosolic Ca(2+) Levels","volume":"7","author":"Sun","year":"2020","journal-title":"Front. Mol. Biosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10577-010-9180-5","article-title":"The Ndc80 complex: Integrating the kinetochore\u2019s many movements","volume":"19","author":"Tooley","year":"2011","journal-title":"Chromosome Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/neu.10050","article-title":"Complementary expression and heterophilic interactions between IgLON family members neurotrimin and LAMP","volume":"51","author":"Gil","year":"2002","journal-title":"J. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1038\/ncomms5804","article-title":"Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis","volume":"5","author":"Tsai","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.neuroscience.2009.10.007","article-title":"Effect of KEPI (Ppp1r14c) deletion on morphine analgesia and tolerance in mice of different genetic backgrounds: When a knockout is near a relevant quantitative trait locus","volume":"165","author":"Drgonova","year":"2010","journal-title":"Neuroscience"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ebiom.2016.05.028","article-title":"Retromer in Osteoblasts Interacts With Protein Phosphatase 1 Regulator Subunit 14C, Terminates Parathyroid Hormone\u2019s Signaling, and Promotes Its Catabolic Response","volume":"9","author":"Xiong","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.2147\/JIR.S353489","article-title":"Role of JAK2\/STAT3 Signaling Pathway in the Tumorigenesis, Chemotherapy Resistance, and Treatment of Solid Tumors: A Systemic Review","volume":"15","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/path.1449","article-title":"WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer","volume":"201","author":"Wissmann","year":"2003","journal-title":"J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1093\/carcin\/bgi379","article-title":"Inactivation of Wnt inhibitory factor-1 (WIF1) expression by epigenetic silencing is a common event in breast cancer","volume":"27","author":"Ai","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Dituri, F., Cossu, C., Mancarella, S., and Giannelli, G. (2019). The Interactivity between TGF\u03b2 and BMP Signaling in Organogenesis, Fibrosis, and Cancer. Cells, 8.","DOI":"10.3390\/cells8101130"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13045-020-00937-8","article-title":"EZH2: A novel target for cancer treatment","volume":"13","author":"Duan","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"258","DOI":"10.4103\/1673-5374.244787","article-title":"Emerging roles for insulin-like growth factor binding protein like protein 1","volume":"14","author":"Li","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1107\/S139900471500927X","article-title":"Structure of the catalytic phosphatase domain of MTMR8: Implications for dimerization, membrane association and reversible oxidation","volume":"71","author":"Yoo","year":"2015","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1091\/mbc.e09-06-0483","article-title":"Novel role of ATPase subunit C targeting peptides beyond mitochondrial protein import","volume":"21","author":"Andreu","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3892\/ijmm.2021.4906","article-title":"Estrogen disorders: Interpreting the abnormal regulation of aromatase in granulosa cells (Review)","volume":"47","author":"Liu","year":"2021","journal-title":"Int. J. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/978-1-4939-9030-6_22","article-title":"The Multifaceted S100A4 Protein in Cancer and Inflammation","volume":"1929","author":"Ambartsumian","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_70","first-page":"1779","article-title":"Identification of HMX1 target genes: A predictive promoter model approach","volume":"19","author":"Boulling","year":"2013","journal-title":"Mol. Vis."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Banciu, A., Banciu, D.D., Mustaciosu, C.C., Radu, M., Cretoiu, D., Xiao, J., Cretoiu, S.M., Suciu, N., and Radu, B.M. (2018). Beta-Estradiol Regulates Voltage-Gated Calcium Channels and Estrogen Receptors in Telocytes from Human Myometrium. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051413"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.cellsig.2005.07.003","article-title":"Selective interactions between G protein subunits and RGS4 with the C-terminal domains of the mu- and delta-opioid receptors regulate opioid receptor signaling","volume":"18","author":"Georgoussi","year":"2006","journal-title":"Cell. Signal."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1186\/gb-2007-8-9-r183","article-title":"The DAVID Gene Functional Classification Tool: A novel biological module-centric algorithm to functionally analyze large gene lists","volume":"8","author":"Huang","year":"2007","journal-title":"Genome Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/s41467-020-14701-6","article-title":"Altered chromatin landscape and enhancer engagement underlie transcriptional dysregulation in MED12 mutant uterine leiomyomas","volume":"11","author":"Moyo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.fertnstert.2018.01.034","article-title":"Next-generation sequencing reveals differentially expressed small noncoding RNAs in uterine leiomyoma","volume":"109","author":"Chuang","year":"2018","journal-title":"Fertil. Steril."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13578-022-00852-0","article-title":"Myometrial oxidative stress drives MED12 mutations in leiomyoma","volume":"12","author":"Li","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Paul, E.N., Burns, G.W., Carpenter, T.J., Grey, J.A., Fazleabas, A.T., and Teixeira, J.M. (2021). Transcriptome Analyses of Myometrium from Fibroid Patients Reveals Phenotypic Differences Compared to Non-Diseased Myometrium. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073618"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1158\/0008-5472.CAN-07-6339","article-title":"Lack of hypoxic response in uterine leiomyomas despite severe tissue hypoxia","volume":"68","author":"Mayer","year":"2008","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3638","DOI":"10.1210\/en.2014-1029","article-title":"ROS are critical for endometrial breakdown via NF-\u03baB-COX-2 signaling in a female mouse menstrual-like model","volume":"155","author":"Wu","year":"2014","journal-title":"Endocrinology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1095\/biolreprod.108.075648","article-title":"Constitutive activation of Beta-catenin in uterine stroma and smooth muscle leads to the development of mesenchymal tumors in mice","volume":"81","author":"Tanwar","year":"2009","journal-title":"Biol. Reprod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/j.fertnstert.2020.06.045","article-title":"Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function","volume":"114","author":"Liu","year":"2020","journal-title":"Fertil. Steril."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"17053","DOI":"10.1073\/pnas.1313650110","article-title":"Paracrine activation of WNT\/beta-catenin pathway in uterine leiomyoma stem cells promotes tumor growth","volume":"110","author":"Ono","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","first-page":"61","article-title":"Extracellular matrix (ECM) activates beta-catenin signaling in uterine fibroids","volume":"155","author":"Ko","year":"2018","journal-title":"Reproduction"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/nsmb.2081","article-title":"Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1","volume":"18","author":"Malinauskas","year":"2011","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_86","first-page":"106","article-title":"Microarray study of gene expression in uterine leiomyoma","volume":"30","author":"Litovkin","year":"2008","journal-title":"Exp. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"8912","DOI":"10.1038\/s41598-022-12899-7","article-title":"Different DNA methylome, transcriptome and histological features in uterine fibroids with and without MED12 mutations","volume":"12","author":"Maekawa","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1093\/humrep\/deh698","article-title":"Gene expression studies provide clues to the pathogenesis of uterine leiomyoma: New evidence and a systematic review","volume":"20","author":"Arslan","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4143\/crt.2004.36.1.31","article-title":"Expression profiling of the cellular processes in uterine leiomyomas: Omic approaches and IGF-2 association with leiomyosarcomas","volume":"36","author":"Bae","year":"2004","journal-title":"Cancer Res. Treat."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.3892\/mmr.2016.5516","article-title":"Upregulation of kallikrein-related peptidase 5 is associated with the malignant behavior of colorectal cancer","volume":"14","author":"Wu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6936","DOI":"10.1074\/jbc.M115.692640","article-title":"Protease-activated Receptor-2 (PAR-2)-mediated Nf-\u03baB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma","volume":"291","author":"Johnson","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e23958","DOI":"10.1002\/jcla.23958","article-title":"Clinical significance of kallikrein 5 as a novel prognostic biomarker in gastric adenocarcinoma","volume":"35","author":"Abuduhadeer","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.biochi.2015.09.002","article-title":"The kallikrein-related peptidase family: Dysregulation and functions during cancer progression","volume":"122","author":"Kryza","year":"2016","journal-title":"Biochimie"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Chuang, T.D., and Khorram, O. (2014). miR-200c Regulates IL8 Expression by Targeting IKBKB: A Potential Mediator of Inflammation in Leiomyoma Pathogenesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095370"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.fertnstert.2015.09.020","article-title":"Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma","volume":"105","author":"Chuang","year":"2016","journal-title":"Fertil. Steril."},{"key":"ref_96","first-page":"138","article-title":"S100A1: Structure, Function, and Therapeutic Potential","volume":"3","author":"Wright","year":"2009","journal-title":"Curr. Chem. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1002\/jcp.25720","article-title":"S100A1 and S100B: Calcium Sensors at the Cross-Roads of Multiple Chondrogenic Pathways","volume":"232","author":"Nesic","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"5973","DOI":"10.1111\/jcmm.15259","article-title":"Extracellular S100A4 as a key player in fibrotic diseases","volume":"24","author":"Li","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00109-007-0301-3","article-title":"S100A4: A common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in diseases?","volume":"86","author":"Schneider","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Dahlmann, M., Kobelt, D., Walther, W., Mudduluru, G., and Stein, U. (2016). S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction. Cancers, 8.","DOI":"10.3390\/cancers8060059"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jsbmb.2005.04.012","article-title":"Aromatase in endometriosis and uterine leiomyomata","volume":"95","author":"Bulun","year":"2005","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1210\/jc.2008-2327","article-title":"High aromatase expression in uterine leiomyoma tissues of African-American women","volume":"94","author":"Ishikawa","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/humupd\/dmac008","article-title":"Epigenomic and enhancer dysregulation in uterine leiomyomas","volume":"28","author":"Mlodawska","year":"2022","journal-title":"Hum. Reprod. Update"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1095\/biolreprod.115.134924","article-title":"The Polycomb Group Protein EZH2 Impairs DNA Damage Repair Gene Expression in Human Uterine Fibroids","volume":"94","author":"Yang","year":"2016","journal-title":"Biol. Reprod."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1177\/1933719116682878","article-title":"Tranilast Inhibits Genes Functionally Involved in Cell Proliferation, Fibrosis, and Epigenetic Regulation and Epigenetically Induces miR-29c Expression in Leiomyoma Cells","volume":"24","author":"Chuang","year":"2017","journal-title":"Reprod. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.xfss.2022.04.005","article-title":"Further characterization of tryptophan metabolism and its dysregulation in fibroids","volume":"3","author":"Chuang","year":"2022","journal-title":"F&S Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.12688\/f1000research.21142.1","article-title":"Falco: High-speed FastQC emulation for quality control of sequencing data","volume":"8","author":"Smith","year":"2019","journal-title":"F1000Res"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkt214","article-title":"The Subread aligner: Fast, accurate and scalable read mapping by seed-and-vote","volume":"41","author":"Liao","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1093\/bioinformatics\/bts477","article-title":"easyRNASeq: A bioconductor package for processing RNA-Seq data","volume":"28","author":"Delhomme","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_112","unstructured":"Iqbal, A., Duitama, C., Metge, F., Rosskopp, D., and Boucas, J. (2022, December 28). Flaski (2.0.3). Zenodo. Available online: https:\/\/zenodo.org\/record\/4890981#.Y-bRDXbMK3A."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein interaction networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ygyno.2014.04.012","article-title":"A high-throughput open-array qPCR gene panel to identify housekeeping genes suitable for myometrium and leiomyoma expression analysis","volume":"134","author":"Almeida","year":"2014","journal-title":"Gynecol. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3742\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:33:37Z","timestamp":1760121217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/4\/3742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":114,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24043742"],"URL":"https:\/\/doi.org\/10.3390\/ijms24043742","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]}}}